Circadian oscillation of hippocampal MAPK activity and cAMP: Implications for memory persistence

Kristin L. Eckel-Mahan, Trongha Phan, Sung Han, Hongbing Wang, Guy C K Chan, Zachary S. Scheiner, Daniel R. Storm

Research output: Contribution to journalArticlepeer-review

284 Scopus citations

Abstract

The mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) signal transduction pathways have critical roles in the consolidation of hippocampus-dependent memory. We found that extracellular regulated kinase 1/2 MAPK phosphorylation and cAMP underwent a circadian oscillation in the hippocampus that was paralleled by changes in Ras activity and the phosphorylation of MAPK kinase and cAMP response element-binding protein (CREB). The nadir of this activation cycle corresponded with severe deficits in hippocampus-dependent fear conditioning under both light-dark and free-running conditions. Circadian oscillations in cAMP and MAPK activity were absent in memory-deficient transgenic mice that lacked Ca2+-stimulated adenylyl cyclases. Furthermore, physiological and pharmacological interference with oscillations in MAPK phosphorylation after the cellular memory consolidation period impaired the persistence of hippocampus-dependent memory. These data suggest that the persistence of long-term memories may depend on reactivation of the cAMP/MAPK/CREB transcriptional pathway in the hippocampus during the circadian cycle.

Original languageEnglish (US)
Pages (from-to)1074-1082
Number of pages9
JournalNature neuroscience
Volume11
Issue number9
DOIs
StatePublished - Sep 2008

ASJC Scopus subject areas

  • General Neuroscience

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